Three second-half goals from AFC Wimbledon saw them run out comfortable winners at Adams Park.
Wyke then turned provider to set up Sammy Moore before Jack Midson notched a penalty after Stewart received his marching orders for a foul on substitute Kevin Saint-Luce.
Debutant Charlie Wyke opened the scoring with a looping header in the 51st minute.
The Dons themselves were reduced to ten men on 90 minutes as Jim Fenlon recklessly lunged in on Josh Scowen.
Steven Craig made an earlier than expected return to the bench after two stages of calves’ blood injections boosted his recovery from a torn thigh muscle.
Marvin McCoy started in the unfamiliar position of left back and with the visitors fielding a 3-5-2 formation was allowed the right to roam forward along with fellow full back Nick Arnold.
McCoy himself was the next to have an attempt as he cut inside Barry Fuller on the left hand side to shoot narrowly wide of the near post.
The Blues signalled their attacking intentions earlier with ex-AFC loanee Knott firing over from the edge of the area.
However, despite scoring just once in their last five games, the visitors showed their threat from set pieces with Sam Wood having to clear off the line from ex-Wanderer Will Antwi’s towering header.
Arnold was the first Blues player to challenge goalkeeper Ross Worner after Knott’s exquisite flick found him just inside the area, however his low curling effort was well fielded by the former Charlton stopper.
Much like in the reverse fixture at Kingsmeadow, 6ft 4in midfielder Harry Pell was a dominating presence in the centre of the park, and his 30-yard drive stung the palms of Matt Ingram just after the half-hour mark.
A first half that lacked fluidity was nearly closed with a goal on the stroke of half time but Wood fired his left-foot drive agonisingly wide of the far post.
However, the Blues failed to build on that opportunity and it was the visitors that flew out of the blocks in the second half and opened the scoring. After a foul on the right-hand side, Sammy Moore’s free-kick was met by debutant Charlie Wyke, whose header into the ground agonisingly looped over Ingram and nestled in the far corner.
The Dons nearly made it two just shy of the hour mark after the increasingly-effective Pell was found on the right-hand side of the box by a clever flick from Jack Midson.
Manager Gareth Ainsworth reacted to falling behind by bringing on strikers Matt McClure and Steven Craig for Jo Kuffour and Knott respectively. The move switched the Blues to a 4-4-2 formation as they looked to take the game to the visitors.
The changes added a sense of urgency to the Blues with Scowen firing over the bar from the edge of the area after good work down the right hand side by Paris Cowan-Hall.
However, it proved to be just a brief injection of energy as the Dons put the game beyond Wanderers with 15 minutes remaining. After Midson had hurled himself at a Luke Moore cross, Wyke held the ball up well before finding Sammy Moore on the edge of the box and he precisely found the bottom corner in front of the Dons fans behind the goal.
The Blues’ misery was then compounded with 10 minutes remaining as substitute Kevin Saint-Luce surged into the box and was felled by Anthony Stewart. Stewart, who had been booked just five minutes before, received his marching orders before Midson sent Ingram the wrong way with a low penalty.
The Dons also failed to finish with their full complement of players on the pitch as Fenlon was shown a straight red for a vicious two-footed lunge at Scowen on the halfway line.
Substitute McClure had a late shot deflected over in added time, but the Blues failed to find a consolation goal as they slipped to 19th place and just four points above the relegation zone.
Wycombe: Ingram; Arnold, McCoy (Morias 80), Johnson, Stewart; Scowen, Lewis; Cowan-Hall, Knott (Craig 66), Wood; Kuffour (McClure 61)
Subs not used:Horlock (GK), Bloomfield, Kretzschmar, Doherty
Sent off:Stewart (81)
AFC Wimbledon: Worner; Antwi, Bennett, Frampton; Fuller, S Moore, Pell, L Moore, Fenlon; Wyke (Sainte-Luce 76), Midson
Subs not used:Brown (GK), Kennedy, Sheringham, Arthur, Porter
Booked:Bennett (41), Antwi (50)
Sent off:Fenlon (90)
Goals:Wyke (51), Moore (75), Midson (pen 82)